FIG. 8.

Activation of electrophilic stress response by OxPLs. Induction of antioxidant genes is initiated by reactive electrophilic compounds via covalent modification of thiol groups in KEAP1 leading to derepression of transcription factor NRF2. OxPLs were shown to induce nuclear accumulation of NRF2, stimulate its binding to promoters of target genes, and elevate mRNA and protein levels of major antioxidant genes. It has to be established whether OxPLs similarly to classical electrophiles form covalent complexes with thiol groups of KEAP1.